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Notes: Background Dithranol (anthralin) has been known to be effective in the treatment of psoriasis for more than 80 years. However, perilesional and uninvolved skin often show irritation during dithranol treatment, which limits its use. As the relapse rate of psoriasis is worsened by adding corticosteroids to a dithranol regimen, the use of topical corticosteroids to reduce dithranol irritation is controversial. Objectives The aim of the present study was to investigate the clinical and cell biological effect of clobetasol-17-propionate 0·05% ointment on dithranol-treated lesional and perilesional skin. Methods For 17 consecutive days, 2% dithranol cream was applied on two test sites. A third site was left untreated on all participating patients (n = 8). All sites consisted of a psoriasis lesion as well as a 3-cm zone of perilesional skin localized on the back. After 1 h, the cream was washed off, and subsequently one of the dithranol-treated sites was treated once a day with clobetasol-17-propionate 0·05% ointment. The second site was treated once daily with the vehicle. On day 17, punch biopsies were taken from all three lesions and from the perilesional zone of all test sites in order to perform an immunohistochemical investigation, using markers to assess proliferation, differentiation and inflammation. Results The SUM score (erythema + induration + scaling) of the lesion treated with dithranol/clobetasol showed a pronounced reduction, which was significantly greater than the SUM score of the lesion treated with dithranol/vehicle. However, the scores of both sites were equal by 6 weeks of follow-up. Comparing the two treated lesions, we observed a lower number of cycling epidermal cells in the dithranol/clobetasol lesion and a significantly lower perivascular dermal score of T lymphocytes. Comparing the perilesional skin of the two treated sites we observed less cycling epidermal cells in the dithranol/clobetasol-treated site. Regarding perilesional differentiation, the interpapillary involucrin expression was higher in the dithranol/clobetasol-treated site. With respect to perilesional inflammation the expression of dermal polymorphonuclear leucocytes, monocytes, macrophages and T lymphocytes in the dermal infiltrate were significantly lower in the dithranol/clobetasol-treated site. Conclusions The addition of clobetasol-17-propionate enhanced the antipsoriatic efficacy of dithranol by interfering with T-cell accumulation and epidermal proliferation. The addition of a corticosteroid reduced perilesional dithranol inflammation at the cellular level, although clinically detectable dithranol erythema was not reduced.

Notes: Summary It is well established that cyclosporin A (CyA), a widely used immunosuppressant in human organ transplantation, is an effective drug in the treatment of psoriasis. Although it has been postulated that the effect of CyA in psoriasis is mediated through antilymphocyte activity, there is also evidence suggesting that CyA exerts a direct cytostatic effect on epidermal keratinocytes, but results of studies relating to the latter have been contradictory.Using immunohistochemical methods we investigated the influence of systemic CyA on proliferation and differentiation in the tape-stripped uninvolved skin of psoriatic patients, a model which provides the opportunity of studying epidermal regeneration in the absence of a significant accumulation of T lymphocytes. We addressed the question of whether CyA (3–5 mg/kg/day) modulates epidermal proliferation and differentiation following standardized injury in uninvolved skin of psoriatic patients. Ten patients with severe psoriasis participated in this study. The dosages of CyA were sufficient to induce a marked and statistically significant improvement (PASI, week 0, 20.5·4.4; PASI, week 16, 4.3 ± 0.6). Before CyA treatment, and during week 16 of treatment, Sellotape stripping was carried out on a 2-cm2 area of the uninvolved skin of psoriatic patients. After 48 h punch biopsies were taken. Immunohistochemical assessment of recruitment of cycling cells (Ki-67), filaggrin, involucrin, T lymphocytes and tenascin, was carried out. We did not find any significant alteration during the treatment period in the tape-stripped uninvolved skin of psoriatic patients. We conclude that epidermal hyperproliferation and abnormal keratinization are not modulated directly by CyA at therapeutic doses in vivo. Furthermore, our study provides indirect evidence that the antipsoriatic effect of CyA is mediated by the immune system.

Notes: Calcitriol, 1α,25 dihydroxycholecalciferol (α.25 (OH)2 D2) is a natural active vitamin D3 metabolite, which has been shown to have antipsoriatic efficacy. In vitro studies have demonstrated that calcitriol influences various aspects of inflammation, epidermal proliferation and keratinization. The aim of the present study was to determine to what extent caicitriol (3 μ/g in white petrolatum) affects these parameters in vivo.Using an immunohistochemical assessment of recruitment of cycling epidermal cells, filaggrin and involucrin expression. T-cell accumulation, polymorphonuclear neutrophil (PMN) accumulation, amount of endothelium and ICAM-1 expression, we demonstrated that: (1) modulation of all these parameters occurred during calcitriol treatment; (ii) there was early reduction of epidermal proliferation and PMN accumulation: (iii) the order of changes was comparable with the response to treatment with calcipotriol.In conclusion, at the cell biological level, calcitriol (3 μ/g in white petrolatum) has a substantial effect on various elements of the psoriatic lesion.

Notes: Summary Background Since its introduction, the effectiveness of dithranol in treating psoriasis has been unequalled by other topical treatments. Out-patient short-contact dithranol treatment is effective with regard to clinical response rate and relapse rate after 1 year. A drawback, however, is the relatively long treatment duration. Objectives To study a dithranol regimen combined with a potent topical corticosteroid with regard to clinical response rate, treatment duration and remission period after clearance. Methods Twelve patients with stable psoriasis vulgaris participated in this study. We treated three comparable psoriasis lesions on the extremities for 39 consecutive days. The first lesion was treated daily with short-contact dithranol cream followed by clobetasol-17-propionate ointment 5 days per week. The second lesion was treated daily with short-contact dithranol cream followed by the vehicle of clobetasol-17-propionate ointment. The third lesion was treated with clobetasol-17-propionate ointment 5 days per week. The patients attended on days 1, 4, 9, 12, 15, 18, 22, 25, 32 and 39 during treatment. We assessed lesional severity scores at each visit and registered the baseline area at the first visit. During the follow up at weeks 2, 4, 6, 10, 14, 19 and 23 we assessed lesional sum scores. We also estimated the area involved in recurrence of the lesion as a percentage of the baseline area. The overall differences between the three treatment curves for the treatment period and follow-up period separately were tested with a likelihood ratio test. Results Differences between the curves of the sum scores during treatment (P 〈 0·001) were mainly due to the different time-course of dithranol monotherapy, which showed a slower decrease in sum score. Differences between the linear trends of the sum score (P 〈 0·001) and the area score (P 〈 0·001) during follow up were due to a different time-course of the combination therapy, which started lower and increased more slowly, suggesting a slower relapse rate with combination therapy. When comparing the follow-up data, it must be kept in mind that the three treatments showed an overall significantly different sum and area score at the start of follow up. Conclusions Intermittent addition of clobetasol-17-propionate ointment enhanced the antipsoriatic efficacy of short-contact, high-dose dithranol therapy in terms of clearing capacity and treatment duration, without shortening remission duration.

Notes: To assess the topical and systemic safety and tolerance of twice-daily application of 3 μg g−1 1α25-dihydroxyvitamin D3 (calcitriol) ointment (Silkis ointment®, Galderma Laboratories) in the long-term treatment of patients suffering from chronic plaque psoriasis, we performed an open-design, multicentre study. Two hundred and fifty-three patients (155 males, 98 females) treated all their psoriatic lesions, except for those on the head and scalp, for up to 78 weeks. No serious adverse events were reported; 37 patients (14·6%) had a transient skin irritation reaction on one or more occasions during the study that resulted in study withdrawal for seven of them. The baseline/endpoint analyses showed no clinically relevant changes in measures of calcium and phosphorus homeostasis and renal function. Slight hypercalcaemia was observed in five (2%) patients; in four of these patients, serum albumin-adjusted total calcium levels normalized during treatment. In conclusion, twice-daily calcitriol 3 μg g−1 ointment is safe and well tolerated in the long-term treatment of chronic plaque psoriasis.

Notes: Numerous investigations have been carried out to describe the cellular biological changes in lesional and symptomless psoriatic ski. Although these studies have increased our knowledge of the pathogenesis of psoriasis, our insight into the relevance of the individual changes in the whole pathogenic process is still limited. Studies on the transition between symptomless and lesional skin are of importance in assessing the pathogenic relevance of the individual aspects. In this paper, the literature is reviewed with respect to the transitional changes; in particular, studies on changes at the margin of the psoriatic lesion and the response of the symptomless skin to standardized injury are reviewed. From the available studies it may be concluded that changes in the stroma (i.e. increased expression of tenascin and increased endothelial alkaline phosphatase activity) are early pathogenic features. The appearance of a predominantly lymphocytic infiltrate, in particular the extravasation of CD4+ T lymphocytes, and the suprabasal expression of keratin 16 are intermediary stages. Relatively late in the pathogenesis are increased recruitment of cycling epidermal nuclei, parakeratosis, decreased expression of filaggrin and premature expression of involucrin. In order to discover the pathogenic relevance of molecules which might have an impact on the development of psoriasis, sequential studies during transition from symptomless to lesional skin are worthwhile.